The androgen receptor (AR) pathway plays a major role in both the pathogenesis
and progression of prostate cancer. In particular, AR is chiefly involved in the development of
castration-resistant prostate cancer (CRPC) as well as in the resistance to the secondgeneration
AR antagonist enzalutamide, and to the selective inhibitor of cytochrome P450
17A1 (CYP17A1) abiraterone. Several small molecules acting as AR antagonists have been
designed and developed so far, also as a result of the ability of cells expressing this molecular
target to rapidly develop resistance and turn pure receptor antagonists into ineffective or event
detrimental molecules. This review covers a survey of most promising classes of non-steroidal
androgen receptor antagonists, also providing insights into their mechanism of action and efficacy
in treating prostate cancer.
Keywords: androgen receptor, castration resistant prostate cancer, antiandrogens, point mutations, PROTACs, AR protein degraders, AR-targeting conjugates.
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